文献类型：期刊文献

中文题名：复方地黄颗粒对帕金森病阴虚动风证模型大鼠脑组织右侧纹状体Wnt/β-catenin信号通路的影响

英文题名：Effect of Fufang Dihuang Granules (复方地黄颗粒) on Wnt/β-catenin Signaling Pathway in Right Striatum of Parkinson’s Disease Model Rats with Yin Deficiency Generating Wind Pattern

作者：梁建庆[1];孙雪[1];梁鹏[2];何建成[3]

第一作者：梁建庆

机构：[1]甘肃中医药大学基础医学院,甘肃省730101;[2]兰州大学第二临床医学院;[3]上海中医药大学基础医学院

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2022

卷号：63

期号：5

起止页码：468

中文期刊名：中医杂志

外文期刊名：Journal of Traditional Chinese Medicine

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(81573899,81660767,82160929);甘肃省教育厅青年博士基金(2021QB-077);甘肃省中医药研究中心开放课题(zyzx-2020-zx20);甘肃中医药大学敦煌医学与转化教育部重点实验室开放课题(DHYX18-08);甘肃中医药大学中青年科研基金(ZQ2015-17);甘肃中医药大学引进人才科研启动基金(2016YJRC-07)。

语种：中文

中文关键词：帕金森病;复方地黄颗粒;阴虚动风证;Wnt/β-catenin信号通路

外文关键词：Parkinson’s disease;Fufang Dihuang Granules(复方地黄颗粒);yin deficiency generating wind pattern;Wnt/β-catenin signaling pathways

摘要：目的探讨复方地黄颗粒治疗帕金森病(PD)阴虚动风证的可能作用机制。方法将175只SPF级雄性SD大鼠随机分为正常组,假手术组,模型组,美多芭组,复方地黄颗粒低、中、高剂量组,每组25只。除正常组、假手术组外,其余各组大鼠给予6-羟基多巴胺(6-OHDA)脑立体注射造模制备PD阴虚动风证大鼠模型。造模成功后复方地黄颗粒低、中、高剂量组分别给予复方地黄颗粒1.75、3.5、7 g/(kg·d)灌胃,美多巴组给予美多芭片150 mg/(kg·d)灌胃,正常组、假手术组及模型组给予生理盐水2 ml灌胃,均每日1次,共28天。观察各组大鼠一般情况及神经行为学测定,检测各组大鼠右侧纹状体组织中Wnt1、低密度脂蛋白受体相关蛋白6(LRP6)、β连环蛋白(β-catenin)、抗卷曲同源物1(Fzd1)、抗糖原合成酶激酶3β(GSK-3β)mRNA及蛋白表达水平。结果与正常组、假手术组大鼠比较,模型组大鼠精神较差,反应迟钝,毛发污秽、枯暗,饮食、活动均减少,体重减轻。与模型组比较,美多芭组、复方地黄颗粒各剂量组大鼠精神、毛发、饮食、活动量等均有所改善,体重增加,且以美多芭组与复方地黄颗粒高剂量组改善较为明显。与正常组、假手术组比较,模型组大鼠旋转圈数增多,Wnt1、P-LRP6、β-catenin、Fzd1蛋白、阳性细胞数及mRNA的表达明显降低,GSK-3β蛋白、阳性细胞数及mRNA表达明显升高(P<0.01)。与模型组比较,美多芭组及复方地黄颗粒各剂量组大鼠旋转圈数均显著减少(P<0.01),右侧纹状体Wnt1、P-LRP6、β-catenin、Fzd1蛋白、阳性细胞数及mRNA水平均明显升高,GSK-3β蛋白、阳性细胞数及mRNA水平明显降低(P<0.05或P<0.01);复方地黄颗粒各剂量组各指标呈剂量依赖性,以复方地黄颗粒高剂量组Wnt1、P-LRP6、β-catenin、Fzd1蛋白、阳性细胞数及mRNA水平最高,GSK-3β蛋白、阳性细胞数及mRNA水平最低(P<0.05或P<0.01)。结论复方地黄颗粒可能通过调控脑组织右侧纹状体Wnt/β-catenin信号通路起到保护多巴胺能神经元的作用,且以高剂量效果最佳。
Objective To explore the mechanism of Fufang Dihuang Granules(复方地黄颗粒,FDG)in treating Parkinson’s disease(PD)model rats with yin deficiency generating wind pattern.Methods 175 SPF male SD rats were randomly divided into normal group,sham operation group,model group,madopar group and FDG low-,medium-and high-dose groups,with 25 rats in each group.Except for the normal group and sham operation group,the rats were injected with 6-OHDA to establish model of PD with yin deficiency generating wind pattern.After successful modeling,the rats in FDG low-,medium-and high-dose groups were given 1.75 g/(kg·d),3.5 g/(kg·d)and7 g/(kg·d)of FDG,respectively,while those in madopar group were administered with 150 m/(kg·d)of madopar;the normal group,sham operation group and model group were given 2 ml of normal saline;the interventions in all the groups were administered by gavage,once daily for 28 days.The general condition and neurobehavior of the rats in each group were observed.The mRNA and protein expression levels of Wntl,low-density lipoprotein receptor-related protein 6(LRP6),β-catenin,anti-frizzled homolog 1(Fzd1),and anti-glycogen synthase kinase 3β(GSK-3β)in the right striatum of rats were detected.Results Compared to the rats in the normal group and the sham operation group,those in the model group were in poorer spirits,unresponsive,with dirty and dull hair,having decreased diet,activity,and weight.Compared to those in the model group,the spirit,hair,diet,activity of the rats were improved in the mgroup and the FDG low-,medium-and high-dose groups,and the body weight increased;additionally,more improvements were seen in the madopar group and the FDG high-dose group.Compared to those in the normal group and the sham operation group,the number of rotations in the model group increased;the positive cells numbers and mRNA expressions of Wntl,P-LRP6,β-catenin,and Fzd1 proteins significantly decreased,while those of GSK-3βsignificantly increased in the model group(P<0.01).Compared to the model group,the madopar group and the three FDG groups had decreased the number of rotations of the rats(P<0.01),increased number of positive cells and mRNA expression levels of Wntl,P-LRP6,β-catenin,and Fzd1 protein in the right striatum,as well as decreased positive cells number and mRNA expression of GSK-3β(P<0.05 or P<0.01).FDG dose-dependency was found in the measured outcomes,and FDG high-dose group had highest number of positive cells and mRNA expressions of Wntl,LRP6,β-catenin and Fzd1,as well as lowest positive cells number and mRNA expression of GSK-3β(P<0.05 or P<0.01).Conclusion FDG may protect dopaminergic neurons by regulating Wnt/β-catenin signaling pathway in the right striatum of brain tissue,and the highest dose has best effect.